Many techniques currently exist for delivering drugs or other medicaments to body tissue. These include topical or transcutaneous administration where the drug is passively absorbed, or caused to pass, into or across the skin or other surface tissue; oral administration; injection directly into body tissue such as through an intramuscular injection or the like; and intravenous administration, which involves introducing a selected drug directly into the blood stream. Transcutaneous drug delivery systems are usually limited to external administration of a drug through the patient's skin or other surface tissue, and thus is inefficient because some of the drug may be absorbed by healthy tissue before it reaches the diseased or damaged area, or carried beyond the diseased or damaged area. Oral administration, injection, and intravenous administration are systemic and so fail to concentrate the drug in a local area.
Transportation of a drug using a localized drug delivery system may be enhanced through means such as iontophoresis. Iontophoresis typically involves an interaction between ionized molecules of a drug and an external electric field, which results in the migration of charged molecules. The migration is accomplished by placing two electrodes across the tissue to be treated and charging the electrodes with a relatively low, direct current (DC), voltage. One of the electrodes acts as a source electrode and is typically in contact with the drug solution. The other electrode acts as a return electrode and may be filled with an electrolyte solution. The electric field generated between the two electrodes causes the charged molecules to migrate from one electrode into the tissues to be treated.
Nevertheless, problems are associated with introducing an electrical current into the body, including muscle stimulation and contraction, as well as pain or other unwanted sensations. More importantly, the problem of cardiac arrhythmia (irregular rhythm) can easily arise when electrical current passes through the heart. The current source causing that problem can originate from an external source, within the heart itself, or adjacent to the heart, such as from a coronary artery.
Intensity (current density), frequency, waveform and duration of the electrical current used in iontophoresis have an effect on whether cardiac arrhythmias and other problems will occur, as well as the magnitude of those reactions. The threshold at which ventricular fibrillation occurs with various transthoracic and intracardiac electrical levels increases with higher frequency currents. The threshold of sensation also increases with higher frequencies. For instance, U.S. Pat. No. 5,087,243 discloses a method which attempts to minimize the risk of iontophoresis-induced arrhythmias. An implanted myocardial iontophoresis patch system is disclosed therein which a pulsed current is supplied to the anodal patch. Electrical activity in the patient's heart is monitored and the iontophoresis current is pulsed on and off in synchronization with ventricular depolarization to avoid the interval during which the heart is vulnerable to electrically induced arrhythmias or unnatural heart rhythms.
What is needed is an improved apparatus for local, transient delivery of gene(s) and/or protein(s), e.g., one which is employed in conjunction with electrical therapy.